Model systems for studying carcinogenesis directly in human target tissues (bronchus, colon, breast, esophagus and pancreatic duct) have been developed to assess the: a) mechanisms of carcinogenesis in human cells; b) variation of carcinogenic susceptibility among individuals; and c) validity of the extrapolation of carcinogenesis data from experimental animals to the human situation. Investigations to date indicate that metabolic pathways and carcinogen-DNA adducts are generally qualitatively similar in both human tissues and tissues of experimental animals in which these chemicals are carcinogenic. Clonal growth and serial passage of human bronchial and esophageal epithelial cells has been achieved. These human cells are being used to study in vitro carcinogenesis, DNA repair, carcinogen metabolism and control of differentiation. Immunoassays that are 100- to 1,000-fold more sensitive than radioimmunoassay and hybridoma-produced monoclonal antibodies to carcinogen-DNA adducts have been developed. These developments provide unique opportunities to detect carcinogen-DNA adducts in human biopsy specimens and to measure the intra- and intergenomic distribution and repair of these adducts at the molecular level.